Effect of beta-adrenergic stimulation on myocardial adenine nucleotide metabolism.

The effects of isoproterenol, propranolol, and compound D600 (o-isopropyl-«-[(Nmethyl-Af-homoveratryl)-Y-aminopropyl]-3,4,5-trimethoxyphenytacetonitrile) on myocardial adenine nucleotide metabolism were studied in rat hearts in situ. Isoproterenol in doses between 0.1 and 25 mg/kg induced an increase in heart rate concomitant with a significant acceleration in the de novo synthesis of adenine nucleotides (ATP, ADP, and AMP) and a diminution in their concentration. The effects of isoproterenol were antagonized by propranolol (1 and 50 mg/kg), which alone caused a reduction in the de novo synthesis of adenine nucleotides without inducing a change in their concentration. Compound D600 (10 mg/kg) brought about a slight elevation in the concentration of adenine nucleotides but did not influence the rate of de novo synthesis. The isoproterenol-induced diminution in adenine nucleotide concentration was prevented by D600; under these conditions, the acceleration of de novo synthesis was attenuated. These findings indicate that de novo synthesis of myocardial adenine nucleotides in the normal and the isoproterenolstimulated heart is regulated not only by a feedback mechanism dependent on the concentration of adenine nucleotides but also by j9-receptor-mediated alterations in carbohydrate metabolism which can cause changes in the size of the available pool of 5-phosphoribosyl1-pyrophosphate.